Antilipemic and anti-inflammatory compositions containing sulfonate derivatives

ABSTRACT

Novel sulfonate derivatives represented by the formula R1SO3CH2CO(CH2)nR2 act to inhibit esterases and chymotripsin and are useful as antilipemic agents, anti-inflammatory agents, immunity controlling agents, etc.

This is a divisional application of Ser. No. 225,979, filed Jan. 19, 1981, now U.S. Pat. No. 4,411,911.

This invention relates to sulfonate derivatives.

The sulfonate derivatives of the present invention are novel compounds represented by the formula

    R.sub.1 SO.sub.3 CH.sub.2 CO(CH.sub.2).sub.n R.sub.2       (I)

wherein R₁ is alkyl having 1 to 4 carbon atoms, alkoxyalkyl having 2 to 6 carbon atoms, aralkyl, cycloalkyl or aryl with or without a substituent (which is alkyl having 1 to 12 carbon atoms, lower alkoxy, halogen, hydroxyl, carboxyl, acetamino, nitro or ethylenedioxymethyl), R₂ is alkyl having 1 to 15 carbon atoms, alkenyl having 2 to 15 carbon atoms, halogen, hydroxyl, lower alkoxy, lower alkoxycarbonyl, acyloxy, carbobenzoxyamino, cycloalkyl having 3 to 6 carbon atoms, cyclic alkylether having 2 to 5 carbon atoms, cyclic alkenylether having 2 to 5 carbon atoms or aryl with or without lower alkyl as substituents, an n is 0 or an integer of 1 to 6.

Examples of the groups represented by R₁ in the formula (I) include: alkyl groups having 1 to 4 carbon atoms, such as methyl, ethyl, propyl and butyl; alkoxyalkyl groups having 2 to 6 carbon atoms, such as ethoxymethyl, methoxyethyl, ethoxypropyl and methoxybutyl; aralkyl groups having 7 to 10 carbon atoms, benzyl, phenethyl and phenylpropyl, and benzyl and phenethyl which have methyl, ethyl or like substituent on the benzene ring; cycloalkyl groups having 5 to 8 carbon atoms, such as cyclopentyl, cyclohexyl and cyclooctyl; and aryl groups, such as phenyl and naphthyl, examples of substituents therefor being alkyl groups having 1 to 12 carbon atoms, such as methyl, propyl, hexyl, decyl and dodecyl, lower alkoxy groups having 1 to 6 carbon atoms, such as methoxy, ethoxy and hexyloxy, and halogen atoms, such as fluorine, chlorine, bromine and iodine, in addition to those already given.

Examples of the groups represented by R₂ in the formula (I) include: alkyl groups having 1 to 15 carbon atoms, such as methyl, ethyl, propyl, hexyl, decyl, dodecyl and pentadecyl; alkenyl groups having 2 to 15 carbon atoms, such as vinyl, allyl, propenyl, butenyl, decenyl and tetradecenyl; halogen atoms, such as fluorine, chlorine, bromine and iodine; lower alkoxy groups having 1 to 5 carbon atoms; lower alkoxycarbonyl groups having 2 to 6 carbon atoms, such as methoxycarbonyl, ethyoxycarbonyl, butoxycarbonyl and pentyloxycarbonyl; acyloxy groups having 2 to 6 carbon atoms, such as acetyloxy, propanoyloxy, butyryloxy and valeryloxy; cycloalkyl groups having 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; cyclic alkylether groups, such as tetrahydrofuranyl and tetrahydropyranyl; cyclic alkenylether groups, such as 2,3-dihydrofuranyl, 2,5-dihydrofuranyl, furanyl, 3,4-dihydro-2H-pyranyl, 3,6-dihydro-2H-pyranyl, 2H-pyranyl, 4H-pyranyl and pyranyl; and aryl groups, such as phenyl and naphthyl, exemplary of substituents therefor being alkyl groups having 1 to 6 carbon atoms. The groups R₂ further include those already specified, such as hydroxyl.

The novel compounds of the present invention have esterase inhibiting activity and chymotripsin inhibiting activity and are useful, for example, as antilipemic agents, anti-inflammatory agents and immunity controlling agents.

The compounds of the formula (I) can be prepared by the following processes.

Process A

A process in which a compound represented by the formula

    N.sub.2 CHCO(CH.sub.2).sub.n R.sub.2                       (II)

wherein R₂ and n are as defined above is reacted with a sulfonic acid compound represented by the formula

    R.sub.1 SO.sub.3 H.mH.sub.2 O                              (III)

wherein R₁ is as defined above, and m is 0 or an integer of 1 or 2.

Process B

A process in which a compound represented by the formula

    XCH.sub.2 CO(CH.sub.2).sub.n R.sub.2                       (IV)

wherein X is fluorine, chlorine, bromine or iodine, and R₂ and n are as defined above is reacted with a metal salt of a sulfonic acid represented by the formula

    R.sub.1 SO.sub.3 H TM (V)

wherein R₁ is as defined above. Examples of metals of such metal salts are sodium, potassium, magnesium, iron, lead, copper, silver, etc.

The reaction of the process A is conducted usually in a solvent, which is not particularly limited insofar as it does not participate in the reaction. Examples of suitable solvents are dimethyl ether, diethyl ether, tetrahydrofuran, dioxane and like ethers, acetonitrile, chloroform, dichloromethane and like non-protonic solvents, petroleum ether, ligroine, etc. The compound (II) and the sulfonic acid compound (III) are used preferably in the ratio of at least one mole of the compound (III) per mole of the compound (II). The reaction proceeds advantageously usually at a temperature of about -10° to about 60° C., preferably at about 0° C. to room temperature. Useful compounds (II), some of which are known and some novel, can be prepared from acid chlorides (VI) and diazomethane by the following known reaction. ##STR1## wherein R₂ and n are as defined above

The reaction of the acid chloride (VI) with diazomethane is conducted usually in a solvent. Useful solvents are those usable for the reaction between the compound (II) and the compound (III). The acid chloride (VI) and diazomethane are used preferably in the ratio of at least about 2 moles of diazomethane per mole of the acid chloride (VI). The reaction proceeds advantageously at a temperature of about -10° C. to room temperature. The compound (II) produced by the reaction, which can be isolated by a usual separating method such as recrystallization or chromatography, is generally usable as contained in the reaction mixture for the subsequent reaction without isolation.

The reaction of the process B is effected in the absence or presence of a solvent. Suitable solvents, although not particularly limited insofar as they do not participate in the reaction, are methanol, ethanol and like lower alcohols, and acetone, acetonitrile, tetrahydrofuran, dioxane, dimethylformamide and like polar solvents. The compound (IV) and the compound (V) are used preferably in an equimolar ratio. The reaction proceeds advantageously generally at room temperature to the boiling point of the solvent.

Useful compounds (IV) for the process B, some of which are known and some novel, can be prepared, for example, by the following reaction. ##STR2## wherein R₂ is as defined above, and M is sodium, potassium or like alkali metal. The reaction between the compound (VII) and the compound (VIII) is effected in the absence or presence of a solvent. Useful solvents, which are not particularly limited provided that they do not participate in the reaction, are methanol, ethanol and like lower alcohols, tetrahydrofuran, dioxane and like polar solvent, acetone, etc. The compound (VII) and the compound (VIII) are used preferably in an equimolar ratio. The reaction is carried out usually at a temperature of about 0° C. to the boiling point of the solvent, preferably at room temperature to about 60° C. The resulting compound (IV) is used as a starting material of the invention, as isolated from, or contained in, the reaction mixture.

The novel compounds (I) prepared by the processes A and B can be isolated by usual methods, such as column chromatography, recrystallization and vacuum distillation.

Among the sulfonate derivatives thus prepared, those in which R₂ is acyloxy can be further converted, if desired, to compounds in which R₂ is hydroxyl when hydrolyzed in the presence of an acid catalyst. This reaction is carried out usually in a solvent, which is not particularly limited provided that it does not participate in the reaction. Suitable solvents are water-containing alcohols, such as methanol, ethanol, etc. Acids useful for the hydrolysis are those usually serviceable as deacylating agents, such as hydrochloric acid, sulfuric acid, nitric acid, acetic acid and hydrobromic acid. The reaction proceeds advantageously usually at -10° to 50° C., preferably about 0° C. to room temperature.

The compounds of the invention represented by the formula (I) can be prepared also by the following process. ##STR3## wherein R₁, R₂ and n are as defined above, but R₂ is not hydroxyl. The reaction between the keto-alcohol (IX) and the sulfonyl chloride (X) is conducted usually in a solvent in the presence of a dehydrochloride agent. The solvent is not particularly limited provided that it does not participate in the reaction. Examples of useful solvents are chloroform, dichloromethane and difluoromethane. Exemplary of useful dehydrochloride agent are pyridine, triethylamine, metal alcoholate, DBU (1,8-diazabicyclo(5,4,0)-7-undecene) and like bases. The keto-alcohol (IX) and the sulfonyl chloride (X) are used preferably in an equimolar ratio. The reaction is carried out at a temperature of -10° to 50° C., preferably at about 0° C. to room temperature.

As already mentioned, the sulfonate compounds of this invention have inhibitory activity on esterases and chymotripsin and are useful as the active components of drugs, such as antilipemic agents, anti-inflammatory agents, immunity controlling agents, etc.

Antilipemic agents containing compounds of the invention will be described below for example, in comparison with those heretofore available.

Hyperlipidemia is known to be a risk factor leading to various adult diseases, such as arteriosclerosis, cardio- and nephro-vascular diseases, diabetes, etc. The drugs for preventing or alleviating hyperlipidemia must have high safety because such drugs are likely to be used for a prolonged period of time in view of the nature of the disease. However, reports have been made on various side effects of nicotinic acid and derivatives thereof, dextran sulfate, and clofibrate and derivatives thereof heretofore widely used as antilipemic agents. Nicotinic acid and its derivatives, for example, produce side effects, such as pruritus and cutaneous flushing due to vasodilatation, gastrointestinal disorders, abnormalities in liver function and glucose intolerance. These drugs have many side effects further because they must be given at a large dose of at least 3 g/day.

Clofibrate, which is typical of widely used antilipemic agents, has recently been reported as having a carcinogenic activity as a serous side effect. Although animal tests or immunological investigations are being carried out by research institutes, the ultimate conclusions still remain to be made, so that clofibrate is clinically in limited use in various countries. In addition to the carcinogenic activity, clofibrate causes an increased sterol discharge, which reportedly increases the likelihood of gallstone formation. Thus the drug is likely to have another side effect.

The antilipemic agents containing compounds of this invention are much more effective than nicotinic acid, derivatives thereof, dextran sulfate, clofibrate and derivatives thereof and have exceedingly low toxicity and therefore very high safety.

The sulfonate compounds of the invention can be formulated into pharmaceutical preparations suited for various routes of administration. Examples of such preparations are tablets, capsules, granules, powders and liquids for oral administration, and suppositories for non-oral administration.

Examples of useful excipients for preparing tablets, capsules, granules and powders are lactose, sucrose, starch, talc, magnesium stearate, crystalline cellulose, methyl cellulose, carboxymethyl cellulose, glycerin, sodium alginate and gum arabic. Also useful for such preparations are binders, such as polyvinyl alcohol, polyvinyl ether, ethyl cellulose, gum arabic, shellac and sucrose, glazing agents, such as magnesium stearate and talc, and usual coloring agents and disintegrators. Tablets can be coated by a known method. Useful liquid preparations are in the form of aqueous or oily suspensions, solutions, syrups, elixir, etc. These preparations are produced by usual methods.

Examples of useful base materials for preparing suppositories are cacao butter, polyethylene glycol, lanolin, fatty acid triglyceride, witepsol (fat, trade mark of Dynamit Nobel A.G. of Germany), etc.

The dose of the drugs according to the invention can not be specifically defined but varies with the symptoms, body weight, age, etc. of the patient. Usually the active component of such drugs is given in an amount of about 50 to about 1500 mg/day for adults at a time or in two to four divided doses. The dose unit such as tablet or capsule preferably contains about 10 to about 1500 mg of the active component.

Given below are examples in which compounds of this invention are prepared, examples of pharmaceutical preparations, tests for determining antilipemic effect and acute toxicity test.

EXAMPLE 1

A 100 ml quantity of diazomethane ether solution (containing 2.8 g of diazomethane) is prepared from 10 g of N-methyl-N-nitrosourea. To the diazomethane ether solution is added dropwise 1.7 g of n-butyl chloride with ice-cooling, and the mixture is thereafter stirred for 30 minutes. Nitrogen gas is passed through the reaction mixture at room temperature to remove the excess of diazomethane therefrom. The ethereal solution is distilled in a vacuum, and the residue is purified by column chromatography (silica gel, developed with chloroform) to give 1.75 g of light yellow oily 1-diazo-2-pentanone (yield 97.8%).

Mass spectrum (abbr. as MS, M⁺): 112

NMR (CDCl₃) δ(PPM): 5.18 s (2H), 2.22 t (2H), 1.80-1.32 m (2H), 0.88 t (3H)

A 1.1 g portion of the 1-diazo-2-pentanone is dissolved in 30 ml of ether, and 1.6 g of ethanesulfonic acid is slowly added to the solution at room temperature. The mixture is stirred until no nitrogen is evolved. After the reaction, the ethereal layer is washed with water, dried over anhydrous sodium sulfate and distilled in a vacuum to remove the solvent. The oily product is purified by column chromatography (silica gel, developed with chloroform) to give 1.0 g of 2-oxopentylethane sulfonate (Compound 1) in the form of a colorless transparent oil (yield 52.6%).

MS (M⁺): 194

NMR (CDCl₃) δ(ppm): 4.70 s (2H), 3.22 q (2H), 2.42 t (2H), 1.90-1.40 m (2H), 1.44 t (3H), 0.92 (3H)

EXAMPLE 2

Compounds 2 to 5 are prepared in the same manner as in Example 1.

EXAMPLE 3

A 1.2 g quantity of 1-diazo-2-pentanone is dissolved in 50 ml of ether, and 2.3 g of benzenesulfonic acid monohydrate is slowly added to the solution at room temperature. The same procedure as in Example 1 is thereafter followed to give 2.0 g of 2-oxopentylbenzene sulfonate in the form of a colorless transparent oil (Compound 6). Yield 77.2%.

MS (M⁺): 242

NMR (CDCl₃) δ(ppm): 7.35-8.00 m (5H), 4.49 s (2H), 2.42 t (2H), 1.80-1.32 m (2H), 0.87 t (3H)

EXAMPLE 4

Compounds 7 to 14 are prepared in the same manner as in Example 3.

EXAMPLE 5

A 1.0 g quantity of 1-diazo-2-pentanone is dissolved in 50 ml of chloroform, and 2.2 g of o-toluene-sulfonic acid is slowly added to the solution. The same procedure as in Example 1 is thereafter repeated to afford 1.37 g of 2-oxopentyl-o-toluene sulfonate in the form of a transparent colorless oil (Compound 29). Yield 59.9%.

MS (M⁺): 256

NMR (CDCl₃) δ(ppm): 7.92 d (1H), 7.70-7.20 m (3H), 4.49 s (2H), 2.68 s (3H), 2.46 t (2H), 1.80-1.40 m (2H), 0.90 t (3H)

EXAMPLE 6

Compounds 26 to 28 and 30 to 33 are prepared in the same manner as in Example 5.

EXAMPLE 7

A 1.0 g quantity of 1-diazo-2-hexanone is dissolved in 50 ml of ether, and 2.5 g of p-methoxybenzenesulfonic acid is slowly added to the solution at room temperature. The same procedure as in Example 1 is thereafter repeated to afford 1.6 g of 2-oxahexyl-p-methoxybenzene sulfonate in the form of a colorless transparent oil (Compound 35). Yield 70.3%.

MS (M⁺) 286

NMR (CDCl₃) δ(ppm): 7.80 d (2H), 6.97 d (2H), 4.44 s (2H), 3.82 s (3H), 2.42 t (2H), 1.70-1.00 m (4H), 0.81 t (3H)

EXAMPLE 8

Compounds 34 and 36 to 42 are prepared in the same manner as in Example 7.

EXAMPLE 9

A 1.0 g quantity of 1-diazo-2-octanone is dissolved in 30 ml of dioxane, and 2.0 g of p-ethyoxybenzenesulfonic acid is slowly added to the solution at room temperature. The mixture is stirred until no nitrogen is evolved. The reaction mixture is distilled in a vacuum to remove the solvent, and the residue is extracted with 50 ml of ether, washed with water and dried over anhydrous sodium sulfate. The dried product is distilled in a vacuum to remove the solvent and obtain an oily product, which is purified by column chromatography (silica gel, developer solvent chloroform), affording 1.26 g of 2-oxooctyl-p-ethoxybenzene sulfonate (Compound 46), m.p. 38° to 39° C. Yield 59.0%.

MS (M⁺): 328

NMR (CDCl₃) δ(ppm): 7.80 d (2H), 6.95 d (2H), 4.44 s (2H), 4.06 q (2H), 2.44 t (2H), 1.60-1.10 m (8H), 0.82 t (3H)

EXAMPLE 10

Compounds 47 to 58 are prepared in the same manner as in Example 9.

EXAMPLE 11

A 1.2 g quantity of 1-diazo-2-undecanone is dissolved in 50 ml of ether, and 1.6 g of p-chlorobenzenesulfonic acid is slowly added to the solution at room temperature. The mixture is stirred until no nitrogen is evolved. The reaction mixture is washed with water, and the ethereal layer is dried over anhydrous sodium sulfate and distilled in a vacuum to remove the solvent. The residue is recrystallized from ether/petroleum ether to give 1.62 g of 2-oxo-undecyl-p-chlorobenzene sulfonate (Compound 68), m.p. 51° to 51.5° C. Yield 75.3%.

MS (M⁺): 360

NMR (CDCl₃) δ(ppm): 7.81 d (2H), 7.46 d (2H), 4.50 s (2H), 2.40 t (2H), 1.70-1.05 m (14H), 0.82 t (3H)

    ______________________________________                                         Elementary analysis:                                                                               C    H                                                     ______________________________________                                         Calcd. for C.sub.17 H.sub.25 ClSO.sub.4 (%):                                                         56.58  6.99                                              Found (%):            56.37  7.29                                              ______________________________________                                    

EXAMPLE 12

Compounds 64 to 67, 69 and 70 are prepared in the same manner as in Example 11.

EXAMPLE 13

A 1.0 g quantity of 1-diazo-2-nonanone is dissolved in 30 ml of ether, and 2.0 g of 2,4,6-trimethylbenzenesulfonic acid dihydrate is slowly added to the solution at room temperature. The same procedure as in Example 1 is thereafter repeated to give 1.4 g of 2-oxononanyl-2,4,6-trimethylbenzene sulfonate in the form of a colorless transparent oil (Compound 77). Yield 69.0%.

MS (M⁺): 340

NMR (CDCl₃) δ(ppm): 6.93 s (2H), 4.38 s (2H), 2.56 s (6H), 2.46 t (2H), 2.25 s (3H), 2.78-1.00 m (10H), 0.82 t (3H)

EXAMPLE 14

Compounds 78 to 88 are prepared in the same manner as in Example 13.

EXAMPLE 15

A 1.0 g quantity of 1-diazo-2-pentanone is reacted with 2.3 g of 2,3,4,6-tetramethyl-benzene-sulfonic acid in 30 ml of ether until nitrogen no longer evolves. The reaction mixture is washed with water, dried and distilled in a vacuum to remove the ether. The residue is recrystallized from ethanol/water, affording 1.6 g of 2-oxopentyl-2,3,4,6-tetramethylbenzene sulfonate (Compound 95), m.p. 49° to 50° C. Yield 60.0%.

MS (M⁺): 298

NMR (CDCl₃) δ(ppm): 6.94 s (1H), 4.38 s (2H), 2.55 s (6H), 2.44 t (2H), 2.24 s (3H), 2.16 s (3H), 1.77-1.35 m (2H), 0.85 t (3H)

EXAMPLE 16

Compounds 93, 94 and 96 to 113 are prepared in the same manner as in Example 15.

EXAMPLE 17

A 1.2 g quantity of 1-chloro-2-pentanone is dissolved in 50 ml of acetone, 1.7 g of potassium iodide is added to the solution, and the mixture is stirred at room temperature for 5 hours. With addition of 2.8 g of silver p-toluenesulfonate, the mixture is stirred at room temperature for 24 hours. The insolubles are filtered off from the reaction mixture, the filtrate is concentrated in a vacuum, and the resulting oily product is purified by column chormatography (silica gel, developer solvent chloroform), affording 2.04 g of 2-oxopentyl-p-toluenesulfonate (Compound 16), m.p. 33° to 35° C. Yield 80.0%.

MS (M⁺): 256

NMR (CDCl₃) δ(ppm): 7.78 d (2H), 7.31 d (2H), 4.43 s (2H), 2.41 s (3H), 2.41 t (2H), 1.80-1.30 m (2H), 0.82 t (3H)

EXAMPLE 18

Compounds 15, and 17 to 25 are prepared in the same manner as in Example 17.

EXAMPLE 19

A 2.2 g quantity of 1-iodo-2-heptanone is reacted with 3.2 g of silver p-ethoxybenzenesulfonate in the same manner as in Example 17. The same procedure as in Example 17 is thereafter repeated to give 2.3 g of 2-oxoheptyl-p-ethoxybenzenesulfonate (Compound 45), m.p. 35° to 35.5° C. Yield 73.2%

MS (M⁺): 314

NMR (CDCl₃) δ(ppm): 7.80 d (2H), 6.96 d (2H), 4.42 s (2H), 4.06 q (2H), 2.42 t (2H), 1.90-1.04 m (6H), 1.40 t (3H), 0.82 t (3H)

EXAMPLE 20

Compounds 43 and 44 are prepared in the same manner as in Example 19.

EXAMPLE 21

A 1.2 g quanity of 1-chloro-2-pentanone is dissolved in 50 ml of acetone, 1.7 g of potassium iodide is added to the solution, and the mixture is stirred at room temperature for 5 hours. With addition of 2.9 g of silver p-hydroxybenzenesulfonate, the mixture is stirred at room temperature for 12 hours. The insolubles are filtered off from the reaction mixture, the filtrate is concentrated in a vacuum, and the concentrate is extracted with 100 ml of chloroform, washed with water and dried over anhydrous sodium sulfate. The dried product is distilled in a vacuum to remove the solvent. The resulting residue is recrystallized from ethanol/water to afford 1.8 g of 2-oxotridecane-p-hydroxybenzenesulfonate (Compound 59), m.p. 85° to 87° C. Yield 70.0%.

MS (M⁺): 258

NMR (CDCl₃) δ(ppm): 7.65 d (2H), 6.82 d (2H), 4.45 s (2H), 2.40 t (2H), 1.80-1.30 m (2H), 0.82 t (3H), 6.80-7.50 b (1H)

EXAMPLE 22

Compounds 60 to 63 are prepared in the same manner as in Example 21.

EXAMPLE 23

A 6.0 g quantity of 1-chloro-2-pentanone is dissolved in 100 ml of acetone, 8.0 g of potassium iodide is added to the solution, and the mixture is stirred at room temperature for 5 hours. The insolubles are filtered off from the reaction mixture, the filtrate is concentrated in a vacuum, and the concentrate is extracted with 100 ml of ether, washed with sodium thiosulfate and dried over anhydrous sodium sulfate. The dried product is distilled in a vacuum to remove the solvent and obtain an oily product, which is then distilled in a vacuum, giving 6.0 g of 1-iodo-2-pentanone, b.p. 96° to 98° C. at 24 to 25 mm Hg. Yield 54.3%.

MS (M⁺): 222

NMR (CDCl₃) δ(ppm): 3.80 s (2H), 2.70 t (2H), 1.65 q (2H), 0.92 t (3H)

A 0.4 g quantity of 1-iodo-2-pentanone is dissolved in 30 ml of acetonitrile, 0.7 g of silver 2,4,6-trimethylbenzenesulfonate is added to the solution, and the mixture is stirred at room temperature for 40 hours. The insolubles are filtered off from the reaction mixture, and the filtrate is concentrated in a vacuum to obtain an oily product, which is then extracted with 50 ml of ether, washed with water and dried over anhydrous sodium sulfate. The dried product is distilled in a vacuum to remove the solvent and obtain a residue, which is then recrystallized from ethanol/water, giving 0.5 g of 2-oxopentyl-2,4,6-trimethylbenzenesulfonate (Compound 73), m.p. 57.5° to 58.5° C. Yield 94.0%.

MS (M⁺): 284

NMR (CDCl₃) δ(ppm): 6.89 s (2H), 4.36 s (2H), 2.60 s (6H), 2.48 t (2H), 2.30 s (3H), 1.80-1.32 m (2H), 0.89 t (3H)

    ______________________________________                                         Elementary analysis:                                                                              C     H                                                     ______________________________________                                         Calcd. for C.sub.14 H.sub.20 SO.sub.4 (%)                                                           59.13  7.09                                               Found (%):           58.95  7.37                                               ______________________________________                                    

EXAMPLE 24

Compounds 71, 72 and 74 to 76 are prepared in the same manner as in Example 23.

EXAMPLE 25

A 2.3 g quantity of 1-chloro-2-dodecanone is dissolved in 100 ml of acetone, 1.7 g of potassium iodide is added to the solution, and the mixture is stirred at room temperature for 5 hours. With addition of 3.3 g of silver 2,3,5,6-tetramethylbenzenesulfonate, the mixture is further stirred at 40° C. for 10 hours. The reaction mixture is treated in the same manner as in Example 17 for purification, giving 2.8 g of 2-oxodecyl-2,3,5,6-tetramethylbenzenesulfonate (Compound 92), m.p. 36° to 37.5° C. Yield 71.5%.

MS (M⁺): 396

NMR (CDCl₃) δ(ppm): 7.18 s (1H), 4.40 s (2H), 2.50 s (6H), 2.24 s (6H), 2.48 t (2H), 1.80-1.00 m (16H), 0.84 t (3H)

EXAMPLE 26

Compounds 89 to 91 are prepared in the same manner as in Example 25.

Table 1 shows Compounds 1 to 162 which are typical of the sulfonate derivatives of this invention represented by the formula (I). In the table, MS stands for mass spectrum, and the NMR values are δ(ppm) values measured in CDCl₃ except that the value for Compound 103 is determined in dimethylformamide-d₆.

The above compounds of this invention are tested by the following methods for antilipemic effect and acute toxicity. The results are also listed in Table 1. In the column of antilipemic effect in the table, the asterisked values indicate the effect achieved by orally giving 200 mg/kg of the compounds concerned, and the unmarked values, the effect attained by orally giving 100 mg/kg. In the same column, "TG" stands for percent triglycerides inhibition and "CS" percent cholesterol inhibition.

1. Antilipemic effect

Seven-week-old male Wistar rats weighing 200 to 220 g are used, 5 rats in each group.

Each compound of the invention (100 mg or 200 mg) is dissolved in 10 ml of an olive oil-cholesterol mixture (containing 15% of cholesterol). The mixture containing the compound is orally given to the rat with a probe at a dose of 10 ml/kg. Two or 8 hours thereafter, 6 ml of whole blood is withdrawn from the descending aorta of the rat under ether anesthesia with a syringe containing heparin. The blood is centrifuged at 5° C. and 3000 r.p.m. to obtain the plasma. The plasma collected after the lapse of 2 hours is used for determining the triglycerides content, and the plasma obtained 8 hours later for determining the total cholesterol content, using a triglycerides measuring kit (trade mark "Triglycerides-B Test Wako," product of Wako Junyaku Co., Ltd., Japan) and a total cholesterol measuring kit (trade mark "Cholesterol Test Wako," product of the same), respectively. The olive oil-cholesterol mixture containing no compound is similarly given to a control group, while no treatment is conducted for a normal group. The triglycerides and total cholesterol contents in the plasma are also determined for these groups in the same manner as is the case with the test groups.

The present hyperlipidemia inhibition achieved by the present compound is given by ##EQU1## in which A is the triglycerides (cholesterol) content of the control group, B is the triglycerides (cholesterol) content of the normal group, and C is the triglycerides (cholesterol) content of the group to which the present compound is given.

The results are given in Table 1, which shows that the tested compounds of the invention achieve an outstanding antilipemic effect.

2. Acute toxicity

Six-week-old male Wistar rats weighing 180 to 200 g are used, 5 rats in each group. Each compound of the invention is suspended in a 30% aqueous solution of polyethylene glycol 6000 and orally given to the rat at the dosage shown in Table 2. The animals are checked for poisoning, body weight and survival to determine the LD₅₀ value.

                                      TABLE 1                                      __________________________________________________________________________     R.sub.1 SO.sub.3 CH.sub.2 COR.sub.2                                                                                               H                                                                              a   b                       A                               D  E   F       G   Anti-lipemic                                                                          I                    Comp.                                                                              B             C             M.P.                                                                              Yield                                                                              NMR     MS  Effect                                                                                LD.sub.50            No. R.sub.1       R.sub.2       (°C.)                                                                      (%) SO.sub.3 CHCO                                                                          (M.sup.+)                                                                          TG  CS (mg/kg)              __________________________________________________________________________     1   C.sub.2 H.sub.5                                                                              CH.sub.2 CH.sub.2 CH.sub.3                                                                   Oil                                                                               52.6                                                                               4.70    194 92  89 >1000                2   C.sub.2 H.sub.5 OCH.sub.2 CH.sub.2 CH.sub.2                                                  "             "  62.2                                                                               4.71    252 65*                              ##STR4##     "             "  67.7                                                                               4.67    248 51*                           4                                                                                 ##STR5##     "             44.5- 45.5                                                                        65.7                                                                               4.50    256 68  52                        5                                                                                 ##STR6##     "             40- 41                                                                            46.0                                                                               4.49    292 86  73 > 2500                 6                                                                                 ##STR7##     "             Oil                                                                               77.2                                                                               4.49    242 90  53 >1000                  7 "             CH.sub.2 (CH.sub.2).sub.2 CH.sub.3                                                           "  61.5                                                                               4.47    256 98  67                      8   "             CH.sub.2 (CH.sub.2).sub.3 CH.sub.3                                                           "  62.3                                                                               4.48    270 87  60 >2000                9   "             CH.sub.2 (CH.sub.2).sub.4 CH.sub.3                                                           "  70.6                                                                               4.49    284 88  62 >3000                10  "             CH.sub.2 (CH.sub.2).sub.7 CH.sub.3                                                           34 70.5                                                                               4.48    327 80  61 >3000                  11                                                                               "                                                                                             ##STR8##     Oil                                                                               60.1                                                                               4.34    270 80  53 >3000                  12                                                                               "             CH.sub.2 CH.sub.2 CH(CH.sub.3).sub.2                                                         "  54.0                                                                               4.44    270 95  63 >2500                13  "             CHCHCH.sub.3  "  21.0                                                                               4.68    240 72                          14  "             CH.sub.2 CH.sub.2 CHCH.sub.2                                                                 "  65.1                                                                               4.49    254 92  62 >2000                  15                                                                                ##STR9##     CH.sub.2 CH.sub.3                                                                            "  74.5                                                                               4.46    242 40  41 >1500                  16                                                                               "             CH.sub.2 CH.sub.2 CH.sub.3                                                                   33-                                                                               80.0                                                                               4.43    256 64  31 >1500                                                35                                             17  "             CH.sub.2 (CH.sub.2).sub.2 CH.sub.3                                                           Oil                                                                               64.5                                                                               4.42    270 61  33 >2000                18  "             CH.sub.2 (CH.sub.2).sub.3 CH.sub.3                                                           "  67.0                                                                               4.46    284 94  40 >3000                19  "             CH.sub.2 (CH.sub.2).sub.4 CH.sub.3                                                           "  75.7                                                                               4.43    298 78  41 >3000                20  "             CH.sub.2 (CH.sub.2).sub.5 CH.sub.3                                                           36-                                                                               68.0                                                                               4.47    312 71  47 >3000                                                37                                             21  "             CH.sub.2 (CH.sub.2).sub.6 CH.sub.3                                                           32-                                                                               70.0                                                                               4.45    326 70* 43*                                                                               >3000                                                33                                             22  "             CH.sub.2 (CH.sub.2).sub.7 CH.sub.3                                                           50-                                                                               71.0                                                                               4.45    340 62*    >3000                                                51                                             23  "             CH.sub.2 (CH.sub.2).sub.8 CH.sub.3                                                           47-                                                                               67.0                                                                               4.45    354 64*    >3000                                                48                                             24  "             CH.sub.2 (CH.sub.2).sub. 10 CH.sub.3                                                         51-                                                                               69.0                                                                               4.43    382 63*    >3000                                                52                                             25  "             CH.sub.2 (CH.sub.2).sub.12 CH.sub.3                                                          58-                                                                               70.0                                                                               4.43    410 62*    >3000                                                59                                               26                                                                               "                                                                                             ##STR10##    Oil                                                                               68.3                                                                               4.54    312 85  72 >4000                  27                                                                               "             CH.sub.2 (CH.sub.2).sub.5 CH(CH.sub.3).sub.2                                                 "  60.0                                                                               4.46    340 59*    >3000                28  "             CH.sub.2 (CH.sub.2).sub.7 CHCH.sub.2                                                         40-                                                                               62.0                                                                               4.44    352 61*    >3000                                                40.5                                             29                                                                                ##STR11##    CH.sub.2 CH.sub.2 CH.sub.3                                                                   Oil                                                                               59.9                                                                               4.49    256 73  30 >1500                  30                                                                               "             CH.sub.2 (CH.sub.2).sub.2 CH.sub.3                                                           "  52.0                                                                               4.50    270 70  36 >1500                31  "             CH.sub.2 (CH.sub.2).sub.4 CH.sub.3                                                           "  66.0                                                                               4.50    298 61  31 >2000                  32                                                                               "                                                                                             ##STR12##    "  58.0                                                                               4.58    312 70  43 >3000                  33                                                                               "             CH.sub.2 (CH.sub.2).sub.5 CH(CH.sub.3).sub.2                                                 "  60.0                                                                               4.49    340 67*    >3000                  34                                                                                ##STR13##    CH.sub.2 CH.sub.2 CH.sub.3                                                                   "  61.8                                                                               4.42    272 72  68 >1500                  35                                                                               "                                                                                             ##STR14##    "  70.3                                                                               4.44    286 87  72 >2000                36  "             CH.sub.2 (CH.sub.2).sub.3 CH.sub.3                                                           "  71.3                                                                               4.43    300 78  79 >2000                37  "             CH.sub.2 (CH.sub.2).sub.5 CH.sub.3                                                           "  69.0                                                                               4.43    328 62  62 >3000                38  "             CH.sub.2 (CH.sub.2).sub.7 CH.sub.3                                                           46-                                                                               73.3                                                                               4.43    356 67*    >4000                                                47                                             39  "             CH.sub.2 (CH.sub.2).sub.9 CH.sub.3                                                           52-                                                                               60.0                                                                               4.44    384 58*    >4000                                                53                                             40  "             CH.sub.2 CH.sub.2 CH(CH.sub.3 ).sub.2                                                        Oil                                                                               71.5                                                                               4.46    300 72  70 >2000                41  "             CH.sub.2 CH.sub.2 CHCH.sub.2                                                                 "  63.0                                                                               4.44    284 82  61 >2000                42  "             CH.sub.2 (CH.sub.2).sub.7 CHCH.sub.2                                                         30-                                                                               60.5                                                                               4.44    368 57*    >4000                                                31.5                                             43                                                                                ##STR15##    CH.sub.2 CH.sub.2 CH.sub.3                                                                   37- 37.5                                                                          68.0                                                                               4.42    286 97  120                                                                               >2000                  44                                                                               "             CH.sub.2 (CH.sub.2).sub.2 CH.sub.3                                                           36-                                                                               76.0                                                                               4.44    300 99  90 >2000                                                36.5                                           45  "             CH.sub.2 (CH.sub.2).sub.3 CH.sub.3                                                           35-                                                                               73.2                                                                               4.42    314 85  80 >3000                                                35.5                                           46  "             CH.sub.2 (CH.sub.2).sub.4 CH.sub.3                                                           38-                                                                               59.0                                                                               4.44    328 65  62 >3000                                                39                                             47  "             CH.sub.2 (CH.sub.2).sub.5 CH.sub.3                                                           41 51.0                                                                               4.44    342 82* 60 >4000                48  "             CH.sub.2 (CH.sub.2).sub.8 CH.sub.3                                                           65-                                                                               59.0                                                                               4.43    384 72* 55 >4000                                                66.5                                             49                                                                               "                                                                                             ##STR16##    Oil                                                                               68.5                                                                               4.55    300 90  96 >2000                  50                                                                               "                                                                                             ##STR17##    "  66.0                                                                               4.52    342 80  94 >4500                  51                                                                               "             CH.sub.2 (CH.sub.2).sub.5 CH(CH.sub.3).sub.2                                                 "  85.0                                                                               4.44    370 70* 62 >4000                52  "             CH.sub.2 CH.sub.2 CHCH.sub.2                                                                 "  65.0                                                                               4.43    298 95  97 >2000                  53                                                                                ##STR18##    CH.sub.2 CH.sub.2 CH.sub.3                                                                   28- 29                                                                            64.3                                                                               4.43    314 61  42 >2000                  54                                                                               "             CH.sub.2 (CH.sub.2).sub.2 CH.sub.3                                                           Oil                                                                               68.3                                                                               4.43    328 48     >2000                55  "             CH.sub.2 (CH.sub.2).sub.3 CH.sub.3                                                           45-                                                                               67.5                                                                               4.42    342 69* 40*                                                                               >3000                                                46                                             56  "             CH.sub.2 (CH.sub.2).sub.5 CH.sub.3                                                           55-                                                                               69.3                                                                               4.43    370 64* 42*                                                                               >3000                                                56                                             57  "             CH.sub.2 (CH.sub.2).sub.7 CH.sub.3                                                           62-                                                                               75.0                                                                               4.44    398 52*    >4000                                                63                                             58  "             CH.sub.2 CH.sub.2 CH(CH.sub.3).sub.2                                                         Oil                                                                               75.0                                                                               4.44    342 61*    >4000                  59                                                                                ##STR19##    CH.sub.2 CH.sub.2 CH.sub.3                                                                   85- 87                                                                            70.0                                                                               4.45    258 70     >3000                  60                                                                               "             CH.sub.2 (CH.sub.2).sub.3 CH.sub.3                                                           81-                                                                               81.0                                                                               4.50    286 83     >3000                                                83                                             61  "             CH.sub.2 (CH.sub.2).sub.6 CH.sub.3                                                           52-                                                                               78.0                                                                               4.51    328 67     >3000                                                53                                             62  "             CH.sub.2 (CH.sub.2).sub.9 CH.sub.3                                                           51-                                                                               75.0                                                                               4.50    370 72*    >3000                                                52                                               63                                                                               "                                                                                             ##STR20##    84- 86                                                                            68.0                                                                               4.62    272 76     >2000                  64                                                                                ##STR21##    CH.sub.2 CH.sub.2 CH.sub.3                                                                   Oil                                                                               81.1                                                                               4.50    276 82  56 >1000                  65                                                                               "             CH.sub.2 (CH.sub.2).sub.2 CH.sub.3                                                           37-                                                                               58.0                                                                               4.50    290 87  49 >1000                                                38                                             66  "             CH.sub.2 (CH.sub.2).sub.3 CH.sub.3                                                           31-                                                                               69.2                                                                               4.50    304 88                                                          32                                             67  "             CH.sub.2 (CH.sub.2).sub.4 CH.sub.3                                                           47-                                                                               66.9                                                                               4.52    318 80     >2000                                                48                                             68  "             CH.sub.2 (CH.sub.2).sub.7 CH.sub.3                                                           51-                                                                               73.5                                                                               4.50    360 62     >3000                                                51.5                                           69  "             CH.sub.2 (CH.sub.2).sub.8 CH.sub.3                                                           53-                                                                               71.0                                                                               4.48    374 77*    >3000                                                53.5                                           70  "             CH.sub.2 CH.sub.2 CH(CH.sub.3).sub.2                                                         29-                                                                               50.0                                                                               4.48    304 82  47 >2000                                                30                                               71                                                                                ##STR22##    CH.sub.3      48- 49                                                                            56.8                                                                               4.40    256 60  82                        72                                                                               "             CH.sub.2 CH.sub.3                                                                            47-                                                                               70.0                                                                               4.38    270 91  90 >3000                                                48                                             73  "             CH.sub.2 CH.sub.2 CH.sub.3                                                                   57.5--                                                                            94.0                                                                               4.36    284 92  90 >3000                                                58.5                                           74  "             CH.sub.2 (CH.sub.2).sub.2 CH.sub.3                                                           33-                                                                               76.4                                                                               4.38    298 77  87 >3000                                                34                                             75  "             CH.sub.2 (CH.sub.2).sub.3 CH.sub.3                                                           Oil                                                                               72.8                                                                               4.35    312 53  60 >3000                76  "             CH.sub.2 (CH.sub.2).sub.4 CH.sub.3                                                           "  70.0                                                                               4.36    326 55  62 >4000                77  "             CH.sub.2 (CH.sub.2).sub.5 CH.sub.3                                                           "  69.0                                                                               4.38    340 80  74 >4000                78  "             CH.sub.2 (CH.sub.2).sub.6 CH.sub.3                                                           30-                                                                               54.0                                                                               4.38    354 56  61 >4000                                                31                                             79  "             CH.sub.2 (CH.sub.2).sub.7 CH.sub.3                                                           34-                                                                               61.3                                                                               4.38    368 61*    >4000                                                35                                             80  "             CH.sub.2 (CH.sub.2).sub.8 CH.sub.3                                                           35-                                                                               87.0                                                                               4.39    382 63*    >4000                                                36                                             81  "             CH.sub.2 (CH.sub.2).sub.9 CH.sub.3                                                           48-                                                                               68.0                                                                               4.39    396 60*    >4000                                                49                                               82                                                                               "                                                                                             ##STR23##    46- 47                                                                            51.0                                                                               4.38    312 56  66 >3000                  83                                                                               "             CH.sub.2 CH.sub.2 CH(CH.sub.3).sub.2                                                         39-                                                                               58.5                                                                               4.34    312 68  71 >3000                                                40                                               84                                                                               "                                                                                             ##STR24##    33- 34                                                                            74.1                                                                               4.48    340 59     >4000                  85                                                                               "             CH.sub.2 (CH.sub.2).sub.5 CH(CH.sub.3).sub.2                                                 Oil                                                                               84.0                                                                               4.39    368 48     >4000                86  "             CH.sub.2 CH.sub.2 CHCH.sub.2                                                                 38-                                                                               61.0                                                                               4.40    296 79  66 >3000                                                39                                             87  "             CH.sub.2 CHCH(CH.sub.2).sub.3 CH.sub.3                                                       Oil                                                                               20.8                                                                               4.44    338 57*                         88  "             CH.sub.2 (CH.sub.2).sub.7 CHCH.sub.2                                                         38-                                                                               63.0                                                                               4.39    380 66*    >4000                                                39                                             89                                                                                  ##STR25##    CH.sub.2 CH.sub.2 CH.sub.3                                                                   59- 60                                                                            70.0                                                                               4.39    2.98                                                                               56*    >3000                  90                                                                               "             CH.sub.2 (CH.sub.2).sub.3 CH.sub.3                                                           Oil                                                                               75.0                                                                               4.40    326 59*    >3000                91  "             CH.sub.2 (CH.sub.2).sub.5 CH.sub.3                                                           "  67.0                                                                               4.39    354 47*    >3000                92  "             CH.sub.2 (CH.sub.2).sub.8 CH.sub.3                                                           36-                                                                               71.5                                                                               4.40    396 43*    >3000                                                37.5                                           93  "             CH.sub.2 CH.sub.2 CHCH.sub.2                                                                 40-                                                                               63.5                                                                               4.39    310 60*    >3000                                                41                                             94  "             CH.sub.2 (CH.sub.2).sub.5 CH(CH.sub.3).sub.2                                                 Oil                                                                               51.0                                                                               4.38    382 51*    >3000                  95                                                                                ##STR26##    CH.sub.2 CH.sub.2 CH.sub.3                                                                   49- 50                                                                            60.0                                                                               4.38    298 96  97 > 3000                 96                                                                               "             CH.sub.2 (CH.sub.2).sub.2 CH.sub.3                                                           32-                                                                               56.0                                                                               4.38    312 68  71 >3000                                                33                                             97  "             CH.sub.2 (CH.sub.2).sub.4 CH.sub.3                                                           42-                                                                               61.0                                                                               4.38    340 55  47 >3000                                                43                                             98  "             CH.sub.2 (CH.sub.2).sub.6 CH.sub.3                                                           36-                                                                               70.4                                                                               4.38    368 70* 71*                                                                               >4000                                                37                                               99                                                                               "                                                                                             ##STR27##    39- 40                                                                            66.3                                                                               4.49    312 72  78 >3000                  100                                                                              "                                                                                             ##STR28##    35- 37                                                                            70.5                                                                               4.47    354 66* 42*                                                                               >4000                  101                                                                              "             CH.sub.2 (CH.sub.2).sub.7 CHCH.sub.2                                                         28-                                                                               59.5                                                                               4.38    394 54*    >4000                                                29                                               102                                                                               ##STR29##    CH.sub.2 CH.sub.2 CH.sub.3                                                                   107- 108                                                                          58.8                                                                               4.48    286 42*    >3000                  103                                                                               ##STR30##    "             118- 119                                                                          52.4                                                                               4.71    299 51*    >3000                  104                                                                               ##STR31##    "             Oil                                                                               61.1                                                                               4.42    410 56*    >3000                  105                                                                               ##STR32##    "             "  42.9                                                                               4.43    314 55*    >3000                  106                                                                               ##STR33##    "             93- 94                                                                            58.0                                                                               4.66    287 60*                           107                                                                               ##STR34##    "             95- 96                                                                            45.1                                                                               4.60    311 75     >1500                  108                                                                               ##STR35##    "             Oil                                                                               64.3                                                                               4.45    290 64     >1500                  109                                                                               ##STR36##    "             62- 64                                                                            57.5                                                                               4.61    292 82*    >2000                  110                                                                               ##STR37##    "             Oil                                                                               58.4                                                                               4.42    288 70                            111                                                                               ##STR38##    "             63- 64                                                                            62.0                                                                               4.40    270 73  51 >2000                  112                                                                               ##STR39##    "             44- 45                                                                            61.0                                                                               4.40    270 80  62 >2000                  113                                                                               ##STR40##    "             80- 81                                                                            65.0                                                                               4.72    345 60     >1500                  114                                                                               ##STR41##    "             Oil                                                                               40.3                                                                               4.45    326 87  76 >3000                  115                                                                               ##STR42##    "             29- 30                                                                            49.0                                                                               4.43    368 67*    >3000                  116                                                                               ##STR43##    "             61 44.0                                                                               4.42    284 90  82 >2000                  117                                                                               ##STR44##    "             55- 56                                                                            50.0                                                                               4.42    284 70  71 >2000                  118                                                                               ##STR45##    "             87- 88                                                                            50.0                                                                               4.38    312 76*    >3000                  119                                                                               ##STR46##    "             65.5- 66.5                                                                        39.0                                                                               4.64    350 67     >2000                  120                                                                               ##STR47##    CH.sub.2 (CH.sub.2).sub.6 CH.sub.3                                                           44.5- 45.5                                                                        55.3                                                                               4.50    386 66*    >2000                  121                                                                               ##STR48##                                                                                    ##STR49##    Oil                                                                               62.4                                                                               4.58    284 63  66 >3000                  122                                                                              "                                                                                             ##STR50##    41 62.4                                                                               4.61    284 65  51 >3000                  123                                                                              "                                                                                             ##STR51##    "  68.9                                                                               4.55    298 67  60 >3000                  124                                                                              "                                                                                             ##STR52##    "  55.0                                                                               4.57    312 62  42 >3000                  125                                                                              "                                                                                             ##STR53##    "  59.0                                                                               4.47    284 68  44 >3000                  126                                                                              "                                                                                             ##STR54##    "  63.5                                                                               4.50    284 61  47 >3000                  127                                                                              "                                                                                             ##STR55##    "  68.0                                                                               4.56    298 92  67 >3000                  128                                                                              "                                                                                             ##STR56##    "  53.0                                                                               4.55    326 62  51 >3000                  129                                                                              "                                                                                             ##STR57##    "  45.5                                                                               4.54    340 66  45 >3000                130 "                                                                                             ##STR58##    "  75.4                                                                               4.60    312 72  51 >3000                  131                                                                               ##STR59##                                                                                    ##STR60##    60 59.5                                                                               4.53    314 110 97 >2000                  132                                                                              "                                                                                             ##STR61##    Oil                                                                               61.6                                                                               4.31    300 87  90 >2000                  133                                                                              "                                                                                             ##STR62##    "  56.5                                                                               4.60    314 111 91 >4500                  134                                                                              "                                                                                             ##STR63##    45- 47                                                                            72.0                                                                               4.57    328 82  65 >4500                  135                                                                              "                                                                                             ##STR64##    27- 28                                                                            55.5                                                                               4.54    342 91  92 >4500                  136                                                                              "                                                                                             ##STR65##    Oil                                                                               68.4                                                                               4.43    314 80  99 >4500                  137                                                                              "                                                                                             ##STR66##    "  63.2                                                                               4.47    328 81  72 >4000                  138                                                                              "                                                                                             ##STR67##    "  65.5                                                                               4.39    314 95  90 >2000                  139                                                                              "                                                                                             ##STR68##    "  80.0                                                                               4.56    328 84  87 >3000                  140                                                                              "                                                                                             ##STR69##    "  69.0                                                                               4.56    356 67  61 >3000                  141                                                                              "                                                                                             ##STR70##    "  51.0                                                                               4.53    370 68  66 >3000                  142                                                                              "                                                                                             ##STR71##    "  56.3                                                                               4.43    328 47     >4000                  143                                                                              "                                                                                             ##STR72##    "  62.0                                                                               4.44    328 62*    >4000                  144                                                                              "                                                                                             ##STR73##    "  58.5                                                                               4.45    342 55*    >4000                  145                                                                              "                                                                                             ##STR74##    "  62.6                                                                               4.44    328 61  62 >3000                  146                                                                              "                                                                                             ##STR75##    "  68.6                                                                               4.56    342 85  77 >4000                  147                                                                               ##STR76##                                                                                    ##STR77##    30- 31                                                                            67.7                                                                               4.51    298 98  72 >3000                  148                                                                              "                                                                                             ##STR78##    51 65.8                                                                               4.50    312 96  80 >3000                  149                                                                              "                                                                                             ##STR79##    35.5- 37                                                                          62.0                                                                               4.38    298 81  67 >3000                  150                                                                              "                                                                                             ##STR80##    48- 49                                                                            70.0                                                                               4.52    312 84  79 >3000                  151                                                                              "                                                                                             ##STR81##    47- 48                                                                            72.4                                                                               4.50    326 83  77 >3000                  152                                                                              "                                                                                             ##STR82##    48- 49                                                                            61.0                                                                               4.50    340 78  69 >4000                  153                                                                              "                                                                                             ##STR83##    Oil                                                                               63.0                                                                               4.33    312 82  83 >4000                  154                                                                              "                                                                                             ##STR84##    "  65.0                                                                               4.40    326 76  70 >4000                  155                                                                              "                                                                                             ##STR85##    29- 30                                                                            58.5                                                                               4.50    326 67  71 >3000                  156                                                                              "                                                                                             ##STR86##    30- 31                                                                            62.3                                                                               4.50    354 58  62  4000                  157                                                                              "                                                                                             ##STR87##    44.5- 45.5                                                                        54.0                                                                               4.50    368 67  66 >4000                  158                                                                              "                                                                                             ##STR88##    Oil                                                                               56.7                                                                               4.39    326 74  70 >4000                  159                                                                              "                                                                                             ##STR89##    "  69.0                                                                               4.42    326 49  51 >4000                  160                                                                              "                                                                                             ##STR90##    "  71.0                                                                               4.41    340 42  40 >4000                  161                                                                              "                                                                                             ##STR91##    "  59.8                                                                               4.39    326 51  56 >3000                  162                                                                              "                                                                                             ##STR92##    31.5- 33                                                                          79.1                                                                               4.52    340 75  77 >4000                __________________________________________________________________________

Given below are typical examples of pharmaceutical preparations of the invention.

Preparation 1

An encapsulated preparation is formulated by enclosing the following composition (500 mg) in each of soft capsules by a usual method.

    ______________________________________                                         Compound 136    250 mg                                                         Olive oil       250 mg                                                         ______________________________________                                    

Preparation 2

Tablets are prepared by a usual method, each from the following composition weighing 406 mg.

    ______________________________________                                         Compound 149           100    mg                                               Soft silicic anhydride 80     mg                                               Crystalline cellulose  140    mg                                               Lactose                80     mg                                               Talc                   2      mg                                               Magnesium stearate     4      mg                                               ______________________________________                                    

Preparation 3

A granular preparation is formulated by a usual method, as enclosed in wrappers each containing the following composition (1000 mg).

    ______________________________________                                         Compound 135      200 mg                                                       Soft silicic anhydride                                                                           170 mg                                                       Crystalline cellulose                                                                            350 mg                                                       Lactose           270 mg                                                       Magnesium stearate                                                                                10 mg                                                       ______________________________________                                    

Preparation 4

Suppositories are prepared by a usual method, each from the following composition weighing 2000 mg.

    ______________________________________                                         Compound 73     1000 mg                                                        Witepsol W-35   1000 mg                                                        ______________________________________                                    

Preparation 5

An elixir preparation is formulated by a usual method, as enclosed in vials each containing the following composition (20 ml).

    ______________________________________                                         Compound 50              300    mg                                             Ethanol                  0.5    ml                                             Granular sugar           2000   mg                                             Nikkol HCO-60 (Nikko Chemicals                                                                          150    mg                                             Co., Ltd.)                                                                     Flavour                  0.01   ml                                             Purified water           q.s.                                                  ______________________________________                                    

Given below are reference examples and examples in which other compounds of the invention are prepared.

REFERENCE EXAMPLE 1

A 100 ml quantity of diazomethane ether solution (containing 2.8 g of diazomethane) is prepared from 10 g of N-methyl-N-nitrosourea. To the diazomethane ether solution is added dropwise 1.6 g of cyclopropylcarbonyl chloride with ice-cooling, and the mixture is thereafter stirred for 30 minutes. Nitrogen gas is passed through the reaction mixture at room temperature to remove the excess of diazomethane therefrom. The ethereal solution is distilled in a vacuum, quantitatively affording cyclopropyl diazomethyl ketone in the form of a light yellow oil (Compound A).

MS (M⁺): 110

H-NMR (CDCl₃) δ(ppm): 5.35 s (1H), 2.35-1.95 m (1H), 1.25-0.08 m (4H)

Compounds B to H listed in Table 2 are also prepared in the same manner as above.

REFERENCE EXAMPLE 2

A 100 ml quantity of diazomethane ether solution (containing 2.8 g of diazomethane) is prepared from 10 g of N-methyl-N-nitrosourea. To the diazomethane ether solution is added dropwise 1.5 g of γ-chloro-n-butyroyl chloride with ice-cooling, and the mixture is thereafter stirred for 30 minutes. Nitrogen gas is passed through the reaction mixture at room temperature to remove the excess of diazomethane therefrom. The ethereal solution is distilled in a vacuum, quantitatively affording γ-chloro-n-propyl diazomethyl ketone in the form of a light yellow oil (Compound I).

MS (M⁺): 146

H-NMR (CDCl₃) δ(ppm): 5.25 s (1H), 3.56 t (2H), 2.50 t (2H), 2.28-1.95 m (2H)

Compounds J to N listed in Table 2 are also prepared in the same manner as above.

EXAMPLE 27

A 1.8 g quantity of 1-diazo-4-cyclohexyl-2-butanone is dissolved in 50 ml of ether, 2.1 g of benzenesulfonic acid monohydrate is slowly added to the solution at room temperature, and the mixture is stirred until nitrogen is no longer evolved. After the reaction, the ethereal layer is washed with water, dried over anhydrous sodium sulfate and distilled in a vacuum to obtain an oily product, which is then recrystallized from ethanol/water, affording 2.0 g of 2-oxo-4-cyclohexyl-butylbenzenesulfonate (Compound 164), m.p. 46° to 47° C. Yield 64.5%.

MS (M⁺): 310

H-NMR (CDCl₃) δ(ppm): 8.10-7.40 m (5H), 4.50 s (2H), 2.44 t (2H), 1.95-0.70 m (13H)

    ______________________________________                                         Elementary analysis:                                                                              C    H                                                      ______________________________________                                         Calcd. for C.sub.16 H.sub.22 SO.sub.4 (%):                                                          61.90  7.14                                               Found (%): 61.74     7.29                                                      ______________________________________                                    

EXAMPLE 28

Compounds 163 and 165 to 171 are prepared in the same manner as in Example 27.

EXAMPLE 29

A 1.52 g quantity of 1-diazo-3-cyclopentylacetone is dissolved in 50 ml of ether, 2.4 g of p-ethoxybenzenesulfonic acid is slowly added to the solution at room temperature, and the mixture is thereafter subjected to the same treatment as in Example 27, giving 2.3 g of 2-oxo-3-cyclopentylpropyl-p-ethoxybenzene sulfonate (Compound 172), m.p. 36° to 36.5° C. Yield 70.5%.

MS (M⁺): 326

H-NMR (CDCl₃) δ(ppm): 7.85 d (2H), 6.98 d (2H), 4.44 s (2H), 4.08 q (2H), 2.47 d (2H), 2.30-0.85 m (12H)

    ______________________________________                                         Elementary analysis:                                                                              C    H                                                      ______________________________________                                         Calcd. for C.sub.16 H.sub.22 SO.sub.5 (%):                                                          58.88  6.79                                               Found (%):           58.61  7.17                                               ______________________________________                                    

EXAMPLE 30

Compounds 173 to 179 are prepared in the same manner as in Example 29.

EXAMPLE 31

A 1.54 g quantity of 4-tetrahydropyranyldiazomethyl ketone is dissolved in 50 ml of tetrahydrofuran, 2.1 g of benzenesulfonic acid monohydrate is slowly added to the solution at room temperature, and the mixture is stirred until nitrogen is no longer evolved. The reaction mixture is distilled in a vacuum to remove the solvent, 100 ml of ether is added to the residue for extraction, and the ethereal layer is washed with water, dried over anhydrous sodium sulfate and distilled in a vacuum. The oily product obtained is recrystallized from petroleum ether, affording 1.7 g of 2-oxo-2-(4-tetrahydropyranyl)-ethylbenzene sulfonate (Compound 180), m.p. 54° to 55° C. Yield 59.9%.

MS (M⁺): 284

H-NMR (CDCl₃) δ(ppm): 8.20-7.45 m (5H), 4.62 s (2H), 4.20-3.80 m (2H), 3.55-3.20 m (2H), 3.00-2.60 m (1H), 1.85-1.45 m (4H)

    ______________________________________                                         Elementary analysis:                                                                              C    H                                                      ______________________________________                                         Calcd. for C.sub.13 H.sub.16 SO.sub.5 (%):                                                          51.99  5.37                                               Found (%):           51.66  5.51                                               ______________________________________                                    

EXAMPLE 32

Compounds 181 to 192 are prepared in the same manner as in Example 31.

EXAMPLE 33

A 1.5 g quantity of 1-diazo-5-chloro-2-n-pentanone is dissolved in 50 ml of ether, 2.1 g of benzenesulfonic acid monohydrate is slowly added to the solution at room temperature, and the mixture is stirred until nitrogen is no longer evolved. After the reaction, the ethereal layer is washed with water, dried over anhydrous sodium sulfate and distilled in a vacuum. The oily product obtained is stirred in ice for crystallization. The crystals are filtered off and recrystallized from ethanol/water to obtain 2.3 g of 2-oxo-5-chloro-n-pentyl-benzene sulfonate (Compound 193), m.p. 39° to 40° C. Yield 81.0%.

MS (M⁺): 276

H-NMR (CDCl₃) δ(ppm): 8.00-7.40 m (5H), 4.49 s (2H), 3.47 t (2H), 2.62 t (2H), 2.15-1.80 m (2H)

    ______________________________________                                         Elementary analysis:                                                                              C    H                                                      ______________________________________                                         Calcd. for C.sub.11 H.sub.13 ClSO.sub.4 (%):                                                        47.74  4.74                                               Found (%):           47.68  5.03                                               ______________________________________                                    

EXAMPLE 34

Compounds 194 to 200 are prepared in the same manner as in Example 1.

EXAMPLE 35

A 1.7 g quantity of 1-diazo-5-methoxycarbonyl-2-n-pentanone is dissolved in 50 cc of tetrahydrofuran, 2.5 g of p-ethoxybenzenesulfonic acid is slowly added to the solution at room temperature, and the mixture is thereafter treated in the same manner as in Example 33 to obtain an oily product, which is then recrystallized from ethanol/water, affording 2.2 g of 2-oxo-5-methoxycarbonyl-n-pentyl-p-ethoxybenzene sulfonate (Compound 201), m.p. 67° to 68° C. Yield 64.0%.

MS (M⁺): 344

H-NMR (CDCl₃) δ(ppm): 7.85 d (2H), 7.00 d (2H), 4.45 s (2H), 4.08 q (2H), 3.64 s (3H), 2.55 t (2H), 2.30 t (2H), 2.05-1.65 m (2H), 1.44 t (3H)

    ______________________________________                                         Elementary analysis:                                                                              C    H                                                      ______________________________________                                         Calcd. for C.sub.15 H.sub.20 SO.sub.7 (%):                                                          52.33  5.86                                               Found (%):           52.35  5.85                                               ______________________________________                                    

EXAMPLE 36

Compounds 202, 203 and 205 to 207 are prepared in the same manner as in Example 35.

EXAMPLE 37

A 3.4 g quantity of 2-oxo-5-acetoxy-2-n-pentyl-2,4,6-trimethylbenzene sulfonate (Compound 207) is dissolved in 20 ml of ethanol, 30 ml of 2N HCl is added to the solution with ice-cooling, and the mixture is stirred for 3 hours at room temperature. The reaction mixture is distilled in a vacuum to remove the ethanol, 50 ml of ether is added to the residue for extraction, and the ethereal layer is dried over anhydrous sodium sulfate and distilled in a vacuum. The resulting oily product is purified by silica gel column chromatography (developed with chloroform) to afford 0.9 g of 2-oxo-5-hydroxy-2-n-pentyl-2,4,6-trimethylbenzene sulfonate (Compound 204) in the form of a colorless transparent oil. Yield 30.2%.

MS (M⁺): 300

H-NMR (CDCl₃) δ(ppm): 6.98 s (2H), 4.05-3.70 m (2H), 3.90 s (2H), 2.76 s (1H), 2.56 s (6H), 2.53 t (2H), 2.05-1.70 m (2H)

Table 3 shows the properties of Compounds 163 to 207 and percent triglycerides inhibition (TG).

                  TABLE 2                                                          ______________________________________                                         R.sub.2 (CH.sub.2).sub.n COCHN.sub.2                                             Comp.                   Prop- HNMR     MS                                    No.                                                                              R.sub.2 n erty          COCHN.sub.2                                                                          (M.sup.+)                                      ______________________________________                                                ##STR93##      0 Oil   5.35     110                                       B                                                                                   ##STR94##      1 "     5.20     152                                       C                                                                                   ##STR95##      0 "     5.25     152                                       D   "               1 "     5.20     166                                     E     "               2 "     5.23     180                                       F                                                                                   ##STR96##      0 "     5.76     140                                       G                                                                                   ##STR97##      0 "     5.30     154                                       H                                                                                   ##STR98##      2 "     5.25     174                                       I   Cl              3 "     5.25     146                                     J     I               3 Oil   5.26     238                                     K     OCOCH.sub.3     " "     5.22     170                                     L     COOCH.sub.3     " "     5.29     170                                     M     OCH.sub.3       " "     5.25     142                                       N                                                                                   ##STR99##      5 "     5.23     261                                     ______________________________________                                    

                                      TABLE 3                                      __________________________________________________________________________     R.sub.1 SO.sub.3 CH.sub.2 CO(CH.sub.2).sub.n R.sub.2                           A   B          n C             D     E   F       G   H                         Comp.                                Yield                                                                              NMR     MS  TG                        No. R.sub.1    n R.sub.2       M.P. (°C.)                                                                    (%) SO.sub.3 CHCO                                                                          (M.sup.+)                                                                          (%)                       __________________________________________________________________________     163                                                                                 ##STR100##                                                                               0                                                                                 ##STR101##   Oil   61.0                                                                               4.61    282                             164                                                                               ##STR102##                                                                               2                                                                                 ##STR103##   46-47 64.5                                                                               4.50    310 98                          165                                                                               ##STR104##                                                                               1                                                                                 ##STR105##   51-52 65.0                                                                               4.46    296                             166                                                                               ##STR106##                                                                               1                                                                                 ##STR107##   Oil   51.5                                                                               4.44    310                             167                                                                               ##STR108##                                                                               2                                                                                 ##STR109##   73.5  68.5                                                                               4.45    324 53                          168                                                                               ##STR110##                                                                               0                                                                                 ##STR111##   124   67.0                                                                               4.82    298                             169                                                                               ##STR112##                                                                               1                                                                                 ##STR113##   92-93 59.5                                                                               4.53    312                             170                                                                               ##STR114##                                                                               0                                                                                 ##STR115##   Oil   34.5                                                                               4.60    270                             171                                                                               ##STR116##                                                                               1                                                                                 ##STR117##   Oil   63.0                                                                               4.43    326                             172                                                                               ##STR118##                                                                               1                                                                                 ##STR119##   36-36.5                                                                              70.5                                                                               4.44    326                             173                                                                               ##STR120##                                                                               0                                                                                 ##STR121##   44-45 58.3                                                                               4.57    326                             174                                                                               ##STR122##                                                                               2                                                                                 ##STR123##   44    53.5                                                                               4.45    354 100                         175                                                                               ##STR124##                                                                               0                                                                                 ##STR125##   82.3  41.2                                                                               4.55    282                             176                                                                               ##STR126##                                                                               0                                                                                 ##STR127##   95-96 67.5                                                                               4.49    324                             177                                                                               ##STR128##                                                                               1                                                                                 ##STR129##   36-37 68.3                                                                               4.40    338                             178                                                                               ##STR130##                                                                               1                                                                                 ##STR131##   92-93 57.4                                                                               4.38    338                             179                                                                               ##STR132##                                                                               0                                                                                 ##STR133##   69.5-70                                                                              55.3                                                                               4.62    316                             180                                                                               ##STR134##                                                                               0                                                                                 ##STR135##   54-55 59.9                                                                               4.62    284                             181                                                                               ##STR136##                                                                               0                                                                                 ##STR137##   103-106                                                                              25.0                                                                               4.03q (J = 9.0)                                                                        284                             182                                                                               ##STR138##                                                                               0                                                                                 ##STR139##   81-83 20.0                                                                               4.02q (J = 8.5)                                                                        300                             183                                                                               ##STR140##                                                                               0                                                                                 ##STR141##   154-155                                                                              50.5                                                                               4.54    300                             184                                                                               ##STR142##                                                                               0                                                                                 ##STR143##   57-58 55.3                                                                               4.53    328                             185                                                                               ##STR144##                                                                               0                                                                                 ##STR145##   106-106.5                                                                            23.0                                                                               4.01q (J = 9.0)                                                                        312                             186                                                                               ##STR146##                                                                               0                                                                                 ##STR147##   63.5-64.5                                                                            63.5                                                                               4.48    326                             187                                                                               ##STR148##                                                                               2                                                                                 ##STR149##   72-73 71.0                                                                               4.42    318 94                          188                                                                               ##STR150##                                                                               2                                                                                 ##STR151##   82-83 68.0                                                                               4.49    338 95                          189                                                                               ##STR152##                                                                               0                                                                                 ##STR153##   87    63.5                                                                               5.20    290                             190                                                                               ##STR154##                                                                               1                                                                                 ##STR155##   55-56 51.0                                                                               4.50    318                             191                                                                               ##STR156##                                                                               0                                                                                 ##STR157##   57-58 40.0                                                                               5.00    280                             192                                                                               ##STR158##                                                                               2                                                                                 ##STR159##   120-121                                                                              60.0                                                                               4.53    348                             193                                                                               ##STR160##                                                                               3 Cl            39-40 81.0                                                                               4.49    276                             194                                                                               ##STR161##                                                                               3 OCH.sub.3     Oil   71.5                                                                               4.49    272                             195                                                                               ##STR162##                                                                               3 OCOCH.sub.3   Oil   61.0                                                                               4.50    300 62                          196                                                                               ##STR163##                                                                               3 COOCH.sub.3   "     70.0                                                                               4.50    300 77.9                        197                                                                               ##STR164##                                                                               5                                                                                 ##STR165##   "     45.5                                                                               4.47    419                             198                                                                               ##STR166##                                                                               3 COOCH.sub.3   "     66.0                                                                               4.48    314                             199                                                                               ##STR167##                                                                               5                                                                                 ##STR168##   47-49 52.0                                                                               4.43    433                             200                                                                               ##STR169##                                                                               3 OCOCH.sub.3   Oil   70.7                                                                               4.49    314                             201                                                                               ##STR170##                                                                               3 COOCH.sub.3   67-68 64.0                                                                               4.45    344                             202                                                                               ##STR171##                                                                               3 Cl            Oil   81.5                                                                               4.42    318                             203                                                                               ##STR172##                                                                               3 I             "     53.5                                                                               4.41    410                             204                                                                               ##STR173##                                                                               3 OH            "     30.2                                                                               3.90    300                             205                                                                               ##STR174##                                                                               3 OCH.sub.3     "     67.5                                                                               4.39    314                             206                                                                               ##STR175##                                                                               3 COOCH.sub.3   "     63.0                                                                               4.43    342                             207                                                                               ##STR176##                                                                               3 OCOCH.sub.3   62.5-63.5                                                                            60.5                                                                               4.40    342                           __________________________________________________________________________

Compounds of the formula (I) of this invention are tested for esterase inhibiting activity and chymotripsin inhibiting activity with the following results.

1. Esterase inhibiting activity

A 10 micromole quantity of methyl butyrate in a 50% ethanol solution is added as a substrate to a specified amount of buffer solution containing 0.1 mole of trishydrochloric acid (pH 8.0). To the mixture is further added a 50% ethanol solution of the compound of the invention, immediately followed by addition of an esterase solution prepared from a purified microsome fraction of the liver of a rat (adjusted to hydrolyze 9 micromoles of methyl butyrate at 37° C. in one hour) as an enzyme solution. The mixture is reacted at 37° C. for 60 minutes.

After the reaction, alkaline hydroxylamine is added to the mixture to form a hydroxamic acid derivative of methyl butyrate, and a ferric salt is added to the derivative. The resulting red color is colorimetrically determined (at a wavelength of 540 nm) to determine the amount of remaining methyl butyrate. The esterase inhibiting ratios of the present compound at least at three concentrations are plotted as ordinate, and the logarithms of the concentrations as abscissa to obtain a line, which gives the 50% inhibition concentration (IC₅₀).

2. Chymotripsin inhibiting activity

Chymotripsin (0.1 unit) serving as an enzyme solution is added to a specified quantity of buffer solution containing 0.1 mole of trishydrochloric acid (pH 8.0). To the mixture is further added a 50% ethanol solution of the compound of the invention so that the resulting mixture contains the compound in a concentration of 1×10⁻⁴ mole. The mixture is reacted at 37° C. for 20 minutes.

On completion of the reaction, 10 micromoles of N-acetyl-L-thyrosine ethyl ester (ATEE) serving as a substrate is added to the mixture, and the resulting mixture is reacted at 37° C. for 30 minutes.

After the completion of the reaction, the amount of remaining ATEE is determined by the same hydroxamic acid method as above. The percent chymotripsin inhibition is given by ##EQU2## wherein A is the amount of hydrolyzed esters in the reaction system not containing the compound of the invention, and B is the amount of hydrolyzed esters in the reaction system containing the present compound.

Table 4 shows the IC₅₀ values of compounds of the invention for esterases and percent chymotripsin inhibition thereof.

Table 4 shows that the compounds of the invention act to inhibit esterases and chymotripsin and are useful as antilipemic agents, anti-inflammatory agents and immunity controlling agents.

                  TABLE 4                                                          ______________________________________                                         Compd.    IC.sub.50 for esterases                                                                      Percent chymotripsin                                   No.       (× 10.sup.-6 mole)                                                                     inhibition                                             ______________________________________                                         1         12.0          --                                                     5         3.6           17                                                     8         0.072         100                                                    9         0.068         96                                                     10        0.0076        14                                                     14        0.52          25                                                     18        1.6           77                                                     19        3.4           100                                                    27        0.67          17                                                     28        0.23          15                                                     31        0.017         100                                                    32        0.35          0.4                                                    37        0.15          91                                                     38        0.10          45                                                     47        0.59          67                                                     50        21            31                                                     56        1.0           50                                                     62        0.029         93                                                     66        2.6           100                                                    73        1.0           13                                                     78        0.00063       72                                                     80        0.000032      55                                                     86        0.12          14                                                     90        0.0026        13                                                     96        0.00016       12                                                     98        0.000027      26                                                     101       0.03          23                                                     111       0.28          4                                                      116       1.3           0                                                      120       0.3           35                                                     129       7             30                                                     130       4             52                                                     134       560           2                                                      135       56            10                                                     137       10            14                                                     138       4.2           67                                                     143       2             79                                                     145       3.3           87                                                     149       1             7                                                      151       32            8                                                      153       0.64          9                                                      158       0.4           17                                                     162       2             32                                                     163       1.6           13                                                     164       2.2           100                                                    165       4.4           90                                                     166       3.5           98                                                     167       3.1           100                                                    169       0.8           --                                                     176       0.8           --                                                     177       0.2           10                                                     179       1.5           32                                                     186       32            --                                                     187       14            100                                                    188       25            100                                                    193       0.82          46.8                                                   194       2.4           3.2                                                    195       26            22.2                                                   196       6.8           65.3                                                   197       30            47                                                     201       170           33                                                     205       1.5           10                                                     ______________________________________                                     

What is claimed is:
 1. An antilipemic composition in the form of a tablet, capsule, granule, powder or liquid for oral administration, or suppository comprising an effective amount of a compound of the formula

    R.sub.1 SO.sub.3 CH.sub.2 CO(CH.sub.2).sub.n R.sub.2

wherein R₁ is alkoxyalkyl having 2 to 6 carbon atoms, phenylalkyl, cycloalkyl or aryl (which is phenyl or naphthyl) with or without a substituent (which is alkyl having 1 to 12 carbon atoms, lower alkoxy, halogen, hydroxyl, carboxyl, acetamido, nitro or ethylenedioxymethyl), R₂ is alkyl having 1 to 15 carbon atoms, alkenyl having 2 to 15 carbon atoms, halogen, hydroxyl, lower alkoxy, lower alkoxycarbonyl, C₂ to C₆ acyloxy, benzyloxycarbonylamino, cycloalkyl having 3 to 6 carbon atoms, cyclic alkylether having 2 to 5 carbon atoms, cyclic alkenylether having 2 to 5 carbon atoms or phenyl or naphthyl with or without lower alkyl as substituent(s), and n is 0 or an integer of 1 to 6, when n is 0 R₂ is not alkyl having 1 to 15 carbon atoms, alkenyl having 2 to 15 carbon atoms, halogen, hydroxyl or lower alkoxy, when n is 0, 1 or 2, R₂ is not phenyl with or without lower alkyl as substituent(s), and a pharmaceutically acceptable carrier.
 2. An anti-inflammatory pharmaceutical composition in the form of a tablet, capsule, granule, powder or liquid for oral administration, or suppository comprising an effective amount of a compound of the formula

    R.sub.1 SO.sub.3 CH.sub.2 CO(CH.sub.2).sub.n R.sub.2

wherein R₁ is alkoxyalkyl having 2 to 6 carbon atoms, phenylalkyl, cycloalkyl or aryl (which is phenyl or naphthyl) with or without a substituent (which is alkyl having 1 to 12 carbon atoms, lower alkoxy, halogen, hydroxyl, carboxyl, acetamido, nitro or ethylenedioxymethyl), R₂ is alkyl having 1 to 15 carbon atoms, alkenyl having 2 to 15 carbon atoms, halogen, hydroxyl, lower alkoxy, lower alkoxycarbonyl, C₂ to C₆ acyloxy, benzyloxycarbonylamino, cycloalkyl having 3 to 6 carbon atoms, cyclic alkylether having 2 to 5 carbon atoms, cyclic alkenylether having 2 to 5 carbon atoms, or phenyl or naphthyl with or without lower alkyl substituent(s), and n is 0 or an integer of 1 to 6, when n is 0, R₂ is not alkyl having 1 to 15 carbon atoms, alkenyl having 2 to 15 carbon atoms, halogen, hydroxyl or lower alkoxy, when n is 0, 1, or 2, R₂ is not phenyl with or without lower alkyl as substituent(s), and a pharmaceutically acceptable carrier.
 3. Composition of claim 1, wherein said cyclic ethers contain 4 or 5 carbon atoms.
 4. A composition of claim 2, wherein the cyclic ethers have 4 to 5 carbon atoms. 